A novel architecture for achieving high drug loading in amorphous spray dried dispersion tablets
| Autor: | Nishant Biswas, Kimberly B. Shepard, Stephanie S. Buchanan, Adam J. Smith, Derrick J Marshall, Christopher D. Craig, Deanna M. Mudie, Aaron M. Stewart, Amanda M. Pluntze, Michael M. Morgen, John M. Baumann, Alyssa Ekdahl, David T. Vodak |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
chemistry.chemical_classification
Supersaturation Materials science Concentration sustainment Physical stability Bioavailability enhancement Spray drying lcsh:RS1-441 Pharmaceutical Science Polymer Dosage form Amorphous solid Bioavailability lcsh:Pharmacy and materia medica Chemical engineering chemistry Solid dosage form Amorphous solid dispersion Eudragit L100 Dispersion (chemistry) Glass transition Research Paper |
| Zdroj: | International Journal of Pharmaceutics: X International Journal of Pharmaceutics: X, Vol 2, Iss, Pp 100042-(2020) |
| ISSN: | 2590-1567 |
| Popis: | Although Amorphous Solid Dispersions (ASDs) effectively increase bioavailability, tablet mass can be high due to the large fraction of excipients needed to stabilize the amorphous drug in the solid state, extend drug supersaturation in solution and achieve robust manufacturability. The aim of this work was to reduce tablet mass of an ASD tablet comprising a low glass transition temperature (Tg), rapidly crystallizing drug without compromising these key attributes. In this approach, erlotinib (Tg = 42 °C, Tm/Tg = 1.4 K/K) was spray dried with the high Tg polymer poly(methyl methacrylate-co-methacrylic acid) (Eudragit® L100, Evonik) (Tg = 187 °C) to facilitate high drug loading while maintaining physical stability. Hydroxypropyl methylcellulose acetate succinate (HPMCAS) (AQOAT® HF, Shin-Etsu) was granulated with the ASD to extend supersaturation in solution. For comparison, a benchmark ASD was spray dried at a lower drug loading with HPMCAS-H (Tg = 119 °C). This High Loaded Dosage Form (HLDF) approach reduced tablet mass by 40%, demonstrated similar physical stability and in vitro performance as the benchmark and exhibited excellent downstream manufacturability. Strategically combining two different polymers in a tablet to maintain physical stability and sustain supersaturation in solution can decrease tablet mass of some low Tg, rapidly crystallizing amorphous drugs. Graphical abstract Unlabelled Image |
| Databáze: | OpenAIRE |
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